Captopril, (S)-1-(3-mercapto-2-methyl-1-oxopropyl)-L-proline, having the structural formula ##STR4## is an orally active angiotensin converting enzyme inhibitor useful for treating hypertension and congestive heart failure. See Ondetti et al. U.S. Pat. No. 4,105,776.
Enalapril, (S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline, having the structural formula ##STR5## is also an orally active angiotensin converting enzyme inhibitor. Enalapril contains the L-alanyl-L-proline dipeptide. A related compound, lisinopril, also possesses oral angiotensin converting enzyme inhibitor activity and contains the L-lysyl-L-proline dipeptide. See Harris et al. U.S. Pat. No. 4,374,829.
Fosinopril sodium, (4S)-4-cyclohexyl-1-[[(R)-[(S)-1-hydroxy-2-methylpropoxy](4-phenylbutyl)-p hosphinyl]acetyl]-L-proline propionate (ester), sodium salt having the structural formula ##STR6## is also an orally active angiotensin converting enzyme inhibitor useful for treating hypertension. See Petrillo U.S. Pat. No. 4,337,201.
Haslanger et al., in U.S. Pat. No. 4,749,688, disclose treating hypertension by administering neutral metalloendopeptidase inhibitors alone or in combination with atrial peptides or angiotensin converting enzyme inhibitors.
Neustadt, in U.S. Pat. No. 5,075,302, discloses that mercaptoacyl amino lactams of the formula ##STR7## wherein Y includes propylene and butylene, R.sup.1 is lower alkyl, aryl or heteroaryl, and R.sup.2 is hydrogen, lower alkyl, lower alkoxy lower alkyl, aryl-lower alkyl or heteroaryl-lower alkyl are endopeptidase inhibitors. Neustadt discloses employing such compounds alone or in combination with angiotensin converting enzyme inhibitors to treat cardiovascular diseases such as hypertension, congestive heart failure, edema and renal insufficiency.
Delaney et al., in U.K. Patent 2,207,351, disclose that endopeptidase inhibitors produce diuresis and natriuresis and are useful alone or in combination with angiotensin converting enzyme inhibitors for the reduction of blood pressure. Delaney et al. include various mercapto and acylmercapto amino acids and dipeptides among their endopeptidase inhibiting compounds.
Flynn et al., in European Patent Application 481,522, disclose dual inhibitors of enkephalinase and angiotensin converting enzyme of the formulas ##STR8## wherein n is zero or one and Z is O, S, --NR.sub.6 -- or ##STR9## Additional tricyclic dual inhibitors are disclosed by Warshawsky et al. in European Patent Applications 534,363, 534,396 and 534,492.
Karanewsky et al., in U.S. Pat. Nos. 4,432,971 and 4,432,972, disclose phosphonamidate angiotensin converting enzyme inhibitors of the formula ##STR10## wherein X is a substituted imino or amino acid or ester.
Karanewsky, in U.S. Pat. No. 4,460,579, discloses angiotensin converting enzyme inhibitors including those of the formula ##STR11## and, in U.S. Pat. No. 4,711,884, discloses angiotensin converting enzyme inhibitors including those of the formula ##STR12## wherein X is a thiazine or thiazepine.